Cerebrovascular disease (CBVD), a leading cause of morbidity and mortality, is linked to cognitive and motor impairment, and depression. Magnetic resonance imaging (MRI) has redefined CBVD in large cohort studies, such as the Cardiovascular Health Study (CHS) and Atherosclerosis Risk in Communities (ARIC). In CHS and ARIC, MRI revealed high prevalences of brain abnormalities, specifically white matter hyperintensities, infarcts, and hemorrhages, in populations without known stroke or transient ischemic attack. Further, overt CBVD, such as stroke, was strikingly less common than covert MRI-defined brain disease. The covert findings were not, however, benign accompaniments of aging as they were associated with impaired motor function and cognition, depression, and a striking increase in the risk of subsequent stroke and death. These studies have convincingly demonstrated that clinically-defined CBVD dramatically underestimates the true population burden of CBVD. Much of what we know about cardiovascular disease in American Indians (AIs) comes from the Strong Heart Study (SHS), a prospective study of 4,549 older adults from 13 tribes followed over 18 years. It conducted physical exams, laboratory and cardiac studies, and chart reviews to describe risk factors, prevalence, and incidence of cardiovascular disease morbidity and mortality. Recent analyses estimated the age- and gender- adjusted stroke incidence in the SHS as 679/100,000 persons, adjusted to the age and sex distribution of the U.S. adult population. This incidence is over twice that observed in the general population indicating AIs are experiencing an epidemic of CBVD. AIs, however, were not included in CHS or ARIC or the other community- based studies of CBVD, and the SHS did not perform MRIs. We will complete a clinical and MRI evaluation to re- assess risk and protective factors and describe MRI-defined CBVD in the SHS. With these data from surviving cohort members, we will address our Specific Aims which are to: 1) estimate the prevalence and quantify the extent of CBVD defined by brain MRI findings, specifically white matter hyperintensities, infarcts, hemorrhages, and cerebral atrophy; 2) assess the relationship of risk factors with prevalent MRI-defined CBVD such as demographic, lifestyle, clinical, laboratory, echocardiographic, and ultrasound measures, and the unique influence of acculturation and degree of Indian heritage; and 3) document the strength of associations of MRI- defined CBVD with motor deficits, cognitive impairment, and depressive symptoms, and establish if they are independent of demographic, lifestyle, and laboratory measures. The elevated stroke rates suggest that AIs may be suffering from a large burden of covert CBVD. As an AI sample in which CVD has been rigorously assessed, the SHS cohort is ideal for investigating CBVD and its manifestations. Of the original cohort of 4,549 members, only ~1,950 members will be alive and able to participate; 283 have died since the last submission. Other opportunities to gain knowledge on CBVD among AIs are not forthcoming. There is an urgent need to initiate this study now since as every year passes, fewer members of the original cohort survive. PUBLIC HEALTH RELEVANCE: Cerebrovascular Disease and its Consequences in the Strong Heart Study Cohort The American Indian population is one of the fastest growing segments of our society. Recent information has shown that American Indians have strokes at least 2-3 times more often as White Americans. The damage created by strokes, and other cerebrovascular diseases, can be seen on an MRI (or brain) scan. MRIs also reveal many silent strokes that are never apparent to the person or their doctor. This study will examine American Indians for damage to the brain caused by both apparent and silent strokes. The American Indian population is experiencing an epidemic of cerebrovascular disease, which given the cost and disability caused by strokes, promises to be a staggering public health issues in the years to come.